TGF-beta expression by allogeneic bone marrow stromal cells ameliorates diabetes in NOD mice through modulating the distribution of CD4+ T cell subsets

Cell Immunol. 2008 May-Jun;253(1-2):23-30. doi: 10.1016/j.cellimm.2008.06.009.

Abstract

BMSCs could promote the regeneration of islet beta-cell, but the status of BMSCs under diabetes is still unknown. Our study verified the effect of allogeneic BMSCs (ICR) transferred into NOD mice on blood glucose and CD4+ T cells subsets function. In vivo experiment, BMSCs could decrease blood glucose, weaken lymphocytes proliferation. In vitro experiment, the distribution of CD4+ T cell subsets was changed after co-culture with BMSCs, resulting in a greater frequency of Treg cells and reduced representation of Th17 cells. After TGF-beta blockade, CD4+ T cells differentiated along a route favoring development of Th17, but not Treg cells. Thus, NOD can be treated by BMSCs which changes the distribution of CD4+ T cells, increases the number of Treg cells, and inhibits the differentiation of Th17 cells. And the positive effects of allogeneic BMSCs in the treatment of NOD mice depend on the regulation of TGF-beta secreted by BMSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology*
  • Bone Marrow Transplantation
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / immunology*
  • Female
  • Insulin / immunology
  • Islets of Langerhans / cytology
  • Islets of Langerhans / immunology
  • Mice
  • Mice, Inbred NOD
  • Stromal Cells / cytology
  • Stromal Cells / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Transforming Growth Factor beta / immunology*
  • Transplantation, Homologous*

Substances

  • Cytokines
  • Insulin
  • Transforming Growth Factor beta